The Role of GRP78/BiP in Apoptosis Regulation and Cancer Progression. A Novel Target for Cancer Diagnosis and Therapy

The Role of GRP78/BiP in Apoptosis Regulation and Cancer Progression. A Novel Target for Cancer Diagnosis and Therapy

Yong Fu

     

бумажная книга



Издательство: Книга по требованию
Дата выхода: июль 2011
ISBN: 978-3-6391-3180-2
Объём: 104 страниц
Масса: 178 г
Размеры(В x Ш x Т), см: 23 x 16 x 1

GRP78, a molecular chaperone at the endoplasmic reticulum (ER), is highly elevated in malignant tumors and correlates with severe pathological grade and poor prognosis. GRP78 affects apoptosis by regulating ER Ca2+ signaling and unfolded protein response, but whether other mechanisms exist remains unknown. Searching for novel partners interacting with GRP78 at the ER, we discovered that BIK selectively forms a complex with GRP78. GRP78 overexpression decreases apoptosis induced by BIK. For breast cancer cells that require BIK to mediate estrogen starvation-induced apoptosis, GRP78 overexpression inhibits estrogen starvation-induced BAX activation, mitochondrial permeability transition, and consequent apoptosis. Further, knockdown of endogenous GRP78 by siRNA sensitizes those cells to estrogen starvation. This effect was substantially reduced when BIK level was reduced by siRNA. Additionally, an in vivo study in a Pten conditional knockout mouse model of prostate cancer reveals that homozygous deletion of Grp78 blocks prostate cancer progression initiated by Pten nullification. Our results provide evidences that GRP78 is critical in apoptosis regulation and cancer progression.

Данное издание не является оригинальным. Книга печатается по технологии принт-он-деманд после получения заказа.